Dermatological

The Rare Responsibility: The Body’s Canvas

Dear Impossible Readers,

The human skin is a remarkable work of art. A single touch can trigger an adrenaline surge and make our hearts race. It acts as a knight in shining armour, shielding us from sunburn and dehydration, defending against infections, regulating temperature, and sensing the external environment. It even allows us to communicate emotions through colour changes and expressions. Conditions like acne or eczema are common and familiar, but there are rare dermatological diseases that manifest in different ways. These illnesses can result from genetic mutations, immune system malfunctions, or abnormal cellular growth. Studying them not only enhances patient care but also uncovers hidden insights into how our skin functions.

A genetic mutation causes harlequin ichthyosis and appears at birth. Newborns are encased in thick, diamond-shaped skin plates that make them highly vulnerable to dehydration and infection. In contrast, pemphigus vulgaris usually develops in adulthood, with the immune system mistakenly attacking the proteins that hold skin cells together, resulting in fragile, painful blisters. Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer that grows slowly from fibroblasts in the dermis. It rarely spreads but requires precise surgery to prevent recurrence. Netherton syndrome combines genetics and immunity, leading to scaly, fragile skin, brittle hair, and severe allergic tendencies. Finally, cutaneous T-cell lymphoma, specifically the mycosis fungoides subtype, shows how malignancy can mimic common eczema-like patches, which may progress over years into plaques, tumours, or systemic disease. These five conditions highlight the remarkable diversity of rare dermatological diseases and emphasise the importance of specialised understanding.

Treating these rare diseases varies greatly depending on their causes. Babies with Harlequin Ichthyosis require intensive care, including hydration, infection prevention, and systemic retinoids to soften their thickened skin. Pemphigus vulgaris is managed by calming the immune system, using corticosteroids, immunosuppressants, or targeted therapies like rituximab to reduce the production of harmful antibodies. DFSP depends on precise surgical removal, with drugs such as imatinib reserved for small residual tumours. Netherton Syndrome is mainly managed through supportive care, emollients, gentle skin hygiene, and emerging biologics to control severe allergies. Cutaneous T-cell Lymphoma requires a staged approach. Early stages may respond to topical treatments and phototherapy, whereas advanced cases might need systemic medications or even stem cell transplantation. Across all these conditions, early recognition and targeted treatment greatly improve outcomes.

Gene therapy and protein replacement may eventually target the underlying defects in Harlequin Ichthyosis and Netherton Syndrome, progressing beyond merely managing symptoms. Autoimmune conditions like Pemphigus Vulgaris are benefiting from new biologics that precisely modulate immune responses with fewer side effects. For cancers such as DFSP and Cutaneous T-cell Lymphoma, targeted therapies and immunotherapies are being refined to eliminate malignant cells while specifically protecting healthy tissue. Overall, research is advancing towards addressing root causes, offering the potential for longer-lasting control and, in some cases, cures.

In clinics, next-generation sequencing panels now routinely identify genetic disorders such as Harlequin Ichthyosis or Netherton Syndrome, reducing the years-long diagnostic delays faced by many families. In autoimmune conditions like Pemphigus Vulgaris, rituximab and other targeted biologics have transformed treatment, often replacing long-term steroid dependence with sustained remission. For DFSP, molecular testing for the COL1A1–PDGFB fusion not only confirms the diagnosis but also guides the use of imatinib, a precision therapy tailored to the tumour’s genetics. In Cutaneous T-cell Lymphoma, newer phototherapy regimens, interferon-based treatments, and clinical trials of checkpoint inhibitors are expanding options beyond palliative care. Meanwhile, international patient registries and skin biobank collaborations enable researchers to share genomic and clinical data, accelerating discoveries that once took decades.

Looking forward to your next vote,
Yours Possibly

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Further Reading

Carver, C.A., Kalesinskas, M. and Ahmed, A.R., 2023. Current biologics in treatment of pemphigus foliaceus: a systematic review. Frontiers in Immunology, 14, p.1267668.
Daniels, P., Muse, M.E., Jaskolka, M., Bebb, G., Bermudez, R. and Crane, J.S., 2025. Treatment of Cutaneous Malignancies With Topical, Oral, and Injectable Medication. StatPearls .
Devata, S. and Wilcox, R.A., 2016. Cutaneous T-cell lymphoma: a review with a focus on targeted agents. American journal of clinical dermatology, 17(3), pp.225-237.
Guri-Lamce, I., AlRokh, Y., Kim, Y., Maeshima, R., Graham, C., Hart, S.L., McGrath, J.A. and Jacków-Malinowska, J., 2024. Topical gene editing therapeutics using lipid nanoparticles:‘gene creams’ for genetic skin diseases?. British Journal of Dermatology, 190(5), pp.617-627.
Herz-Ruelas, M.E., Chavez-Alvarez, S., Garza-Chapa, J.I., Ocampo-Candiani, J., Cab-Morales, V.A. and Kubelis-López, D.E., 2021. Netherton syndrome: case report and review of the literature. Skin Appendage Disorders, 7(5), pp.346-350.
Hwu, W.L., 2024. Gene therapy for ultrarare diseases: a geneticist’s perspective. Journal of Biomedical Science, 31(1), p.79.
Jafarzadeh, A., Behrangi, E., Khosravi, M., Falakeh, S., Amiri, J.K. and Goodarzi, A., 2025. Emerging treatments for dermatologic diseases in infants, children, and adolescents: a systematic review of clinical trials on biologics and small molecule inhibitors. Inflammopharmacology, pp.1-56.
Jozwik, M., Bednarczuk, K. and Osierda, Z., 2024. Dermatofibrosarcoma protuberans: an updated review of the literature. Cancers, 16(18), p.3124.
Khandelwal, K., Jajoo, V., Bajpai, K., Madke, B., Prasad, R., Wanjari, M.B., Munjewar, P.K., Taksande, A.B., KHANDELWAL, K., Wanjari, M. and Munjewar, P., 2023. Rituximab in pemphigus vulgaris: a review of monoclonal antibody therapy in dermatology. Cureus, 15(6).
Lee, A., 2025. Prademagene Zamikeracel: First Approval. Molecular Diagnosis & Therapy, 29(5), pp.701-704.
Lisińska, W., Cegiełka, P., Zalewska, Z., Bien, N., Sobolewska-Sztychny, D., Narbutt, J. and Lesiak, A., 2025. Gene Therapies in Dermatological Diseases: A Breakthrough in Treatment. International Journal of Molecular Sciences, 26(14), p.6592.
López, E., Cabrera, R. and Lecaros, C., 2024. Targeted therapy for immune mediated skin diseases. What should a dermatologist know?. Anais Brasileiros de Dermatologia, 99, pp.546-567.
Mocarska, M., Muciek, A., Dolinkiewicz, J., Maryńczak, A.M., Nitschke, N., Strakowska, K., Opalska, L. and Orłowska, A.M., 2025. Netherton Syndrome: A Comprehensive Literature Review of Pathogenesis, Clinical Manifestations, and Therapeutic Strategies. Journal of Mother and Child, 29(1), pp.106-113.
Navarrete-Dechent, C., Mori, S., Barker, C.A., Dickson, M.A. and Nehal, K.S., 2019. Imatinib treatment for locally advanced or metastatic dermatofibrosarcoma protuberans: a systematic review. JAMA dermatology, 155(3), pp.361-369.
Nouwen, A.E., Schappin, R., Nguyen, N.T., Ragamin, A., Bygum, A., Bodemer, C., Dalm, V.A. and Pasmans, S.G., 2022. Outcomes of systemic treatment in children and adults with Netherton syndrome: a systematic review. Frontiers in Immunology, 13, p.864449.
Quadri, I., Reneau, J.C., Hanel, W. and Chung, C.G., 2023. Advancements in the treatment of mycosis fungoides and Sézary syndrome: monoclonal antibodies, immunotherapies, and Janus kinase inhibitors. Frontiers in immunology, 14, p.1291259.
Rajpopat, S., Moss, C., Mellerio, J., Vahlquist, A., Gånemo, A., Hellstrom-Pigg, M., Ilchyshyn, A., Burrows, N., Lestringant, G., Taylor, A. and Kennedy, C., 2011. Harlequin ichthyosis: a review of clinical and molecular findings in 45 cases. Archives of dermatology, 147(6), pp.681-686.
Tsivilika, M., Kavvadas, D., Karachrysafi, S., Sioga, A. and Papamitsou, T., 2022. Management of harlequin ichthyosis: A brief review of the recent literature. Children, 9(6), p.893.